Controlling the morphology of nanostructured silicon is critical to improving the structural stability and electrochemical performance in lithium-ion batteries. The use of removable or sacrificial templates is an effective and easy route to synthesize hollow materials. Herein, we demonstrate the synthesis of mesoporous silicon hollow nanocubes (m-Si HCs) derived from a metal-organic framework (MOF) as an anode material with outstanding electrochemical properties. The m-Si HC architecture with the mesoporous external shell (∼15 nm) and internal void (∼60 nm) can effectively accommodate volume variations and relieve diffusion-induced stress/strain during repeated cycling. In addition, this cube architecture provides a high electrolyte contact area because of the exposed active site, which can promote the transportation of Li ions. The well-designed m-Si HC with carbon coating delivers a high reversible capacity of 1728 mAhg(-1) with an initial Coulombic efficiency of 80.1% after the first cycle and an excellent rate capability of >1050 mAhg(-1) even at a 15 C-rate. In particular, the m-Si HC anode effectively suppresses electrode swelling to ∼47% after 100 cycles and exhibits outstanding cycle stability of 850 mAhg(-1) after 800 cycles at a 1 C-rate. Moreover, a full cell (2.9 mAhcm(-2)) comprising a m-Si HC-graphite anode and LiCoO2 cathode exhibits remarkable cycle retention of 72% after 100 cycles at a 0.2 C-rate.